Abstract

Triple-negative breast cancer is one of the most challenging subtypes to treat because it lacks expression of the established molecular targets: estrogen receptor; progesterone receptor; and human epidermal growth factor receptor 2, explained Agnieszka Witkiewicz from the Thomas Jefferson University Hospital in Philadelphia, Pennsylvania.

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In the present study, Witkiewicz and team examined 97 patients with triple-negative breast cancer, of whom 73 were White and 24 were African-American.

They evaluated insulin-like growth factor 1 receptor (IGF-1R) protein expression by immunohistochemistry, and IGF-1R gene copy number by chromogenic in situ hybridization in each of the patients.

"IGF-1R has a key regulatory role in malignancy and is the target of several drugs currently tested in clinical trials," noted Witkiewicz. It has already been associated with estrogen receptor-positive breast cancer, she added.

The researchers found that IGF-1R was overexpressed in 25% of the patients examined, and IGF-1R protein overexpression correlated significantly with gene amplification.

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In addition, low expression of IGF-1R was significantly associated with lymph node metastasis, while high expression showed a borderline association with lower tumor size.

Among patients younger than 55 years, IGF-1R overexpression was associated with longer survival (hazard ratio 0.13). However, in older patients, there were no significant survival differences between those with low and high IGF-1R expression.

Since IGF-1R blockade has been a successful therapeutic approach in sarcomas, Witkiewicz suggested that there might be potential to target this receptor in this breast cancer subtype as well.

"For now, we know that it is there and we know it is a marker of better prognosis," she said. "The next step is to learn if triple-negative breast cancer patients benefit from targeting IGF-1R."

The study findings were presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development held in Denver, Colorado, USA.